FHL1-interacting proteins involved in cancer progression
| Protein | Interaction domain | Function | Reference |
|---|---|---|---|
| Smad2 | n.d. | FHL increases Smad2/3 phosphorylation, enhances interactions of Smad2/3 and Smad4 in a CK1δ-depedent manner | 52 |
| Smad3 | n.d. | 52 | |
| Smad4 | n.d. | 39,52 | |
| Casein kinase 1, delta (CK1δ) | n.d. | 52 | |
| Receptor interacting protein of 140 kDa (RIP140) | All domains of FHL1 | FHL1 and RIP140 synergistically regulate transcription of estrogen signaling | 38 |
| Estrogen receptor α (ERα) | ERα (1–185) fragment containing the AF1 domain; LIM domains 1, 2 and 3 | FHL1 inhibits the transcriptional activities of ERα and ERβ | 54 |
| Estrogen receptor β (ERβ) | 1–145 aa of ERβ containing N-terminal AF1 domain | 54 | |
| AKT | n.d. | FHL1 inhibits ERα activity through repression of AKT phosphorylation | 58 |
| p300 | n.d. | FHL1 binds to p300/CBP, disrupting binding with HIF-1α | 53 |
| CBP | n.d. | 53 | |
| HIF1α | HIF1α region containing basic helix-loop-helix (bHLH) motif and PER-ARNT-SIM domain; A single LIM domain | FHL1-3 inhibits HIF1α -dependent VEGF promoter activity and VEGF expression | 54 |
| CHK2 | CHK2 (220–356 aa) containing the N-terminal portion of the protein kinase domain, an 11 aa motif, namely W/FHwwCFwCwwC (eLIM) | FHL1 inhibits CDC25 phosphorylation by forming a complex with CHK2 and CDC25, and sequesters CDC25 in the cytoplasm through interactions with 14-3-3 | 68 |
| CDC25 | CDC25C (328 and 383 aa) containing a partial catalytic domain; eLIM | 68 | |
| 14-3-3 | (100–255 aa) of 14-3-3 containing the target binding pocket | 68 | |
| Src | Kinase domain of Src; LIM4 domain | Src phosphorylates FHL1, leading to a switch in activity from tumor suppressor to promoter. Kindlin-2 competes with Src for binding to FHL1 | 40 |
| Kindlin-2 | FERM domain of kindlin-2; LIM4 domain | 40 |